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Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.  相似文献   
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BackgroundLittle is known of possible gender differences in treatment of periampullary tumours and outcome after pancreatoduodenectomy (PD), and the aim of this study was therefore to investigate any variances from national multicentre perspective.MethodsData from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients diagnosed with a periampullary tumour from 2012 throughout 2017 was collected. The material was analysed in two groups, men and women, for palliative treatment and curative intended resection.ResultsA total of 5677 patients were included, 2906 (51%) men and 2771 (49%) women. Women were older than men, 72 (65–78) years vs. 70 (64–76), p < 0.001. A lesser proportion of women were planned for resection (1131 (41%) vs. 1288 (44%), p = 0.008), but after adjusting for age and tumour location no difference was seen. Postoperative morbidity was equal, but women had significantly better long-term survival than men. The survival was equal for palliative men and women.ConclusionNo gender bias could be established when analysing treatment for periampullary tumours in Sweden, even though less women were offered surgery. Data suggest that even though women were older they tolerate surgery well and hence offering PD at a higher age for women could be suggested.  相似文献   
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Fear is central to conceptualizations of weight and shape-focused eating disorders. The current study will examine the reliability and validity of a test meal paradigm that varies perceptions of fat content to manipulate fear. Undergraduate women with elevated eating pathology (N = 96) will be randomized to one of three test meal conditions: two “low” fat yogurts, two “high” fat yogurts, or one “high” fat and one “low” fat yogurt. In actuality, all yogurts will have the same fat content. Supporting reliability, we hypothesize that self-reported fear and electrodermal activity (psychophysiological index of fear-related arousal) will exhibit good test–retest reliability over a 48-hr period in the “high” fat/“high” fat and “low” fat/“low” fat conditions. Supporting construct validity, self-reported fear and electrodermal activity will be elevated during the “high” versus “low” fat condition and responses to the “high" fat condition will correlate with fear of food, eating, and weight gain. Supporting discriminant validity, self-reported disgust and anger will be comparable in the “high” and “low” fat conditions and will exhibit weak correlations with trait measures of disgust and anger. This experimental paradigm will allow researchers to manipulate fear in order understand the mechanisms by which fear maintains eating pathology.  相似文献   
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Background

Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy.

Methods

Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25–60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1–3 L/min.

Results

Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH2O and pressure support 0–0.6 cmH2O. In contrast, 1–3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH2O during simulated airway obstruction.

Conclusions

Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.  相似文献   
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Akbil  Bengisu  Meyer  Tim  Stubbemann  Paula  Thibeault  Charlotte  Staudacher  Olga  Niemeyer  Daniela  Jansen  Jenny  Mühlemann  Barbara  Doehn  Jan  Tabeling  Christoph  Nusshag  Christian  Hirzel  Cédric  Sanchez  David Sökler  Nieters  Alexandra  Lother  Achim  Duerschmied  Daniel  Schallner  Nils  Lieberum  Jan Nikolaus  August  Dietrich  Rieg  Siegbert  Falcone  Valeria  Hengel  Hartmut  Kölsch  Uwe  Unterwalder  Nadine  Hübner  Ralf-Harto  Jones  Terry C.  Suttorp  Norbert  Drosten  Christian  Warnatz  Klaus  Spinetti  Thibaud  Schefold  Joerg C.  Dörner  Thomas  Sander  Leif Erik  Corman  Victor M.  Merle  Uta  Kurth  Florian  von Bernuth  Horst  Meisel  Christian  Goffinet  Christine 《Journal of clinical immunology》2022,42(6):1111-1129
Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...  相似文献   
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